The present invention relates to magnetic resonance imaging (xe2x80x9cMRIxe2x80x9d) and MR spectroscopy using hyperpolarized noble gases. More particularly, the present invention relates to imaging techniques using dissolved phase noble gases.
Conventionally, MRI has been used to produce images by exciting the nuclei of hydrogen molecules (present in water protons) in the human body. However, it has recently been discovered that polarized noble gases can produce improved images of certain areas and regions of the body which have heretofore produced less than satisfactory images in this modality. Polarized Helium 3 (xe2x80x9c3Hexe2x80x9d) and Xenon-129 (xe2x80x9c129Xexe2x80x9d) have been found to be particularly suited for this purpose. See U.S. Pat. No. 5,545,396 to Albert et al., entitled xe2x80x9cMagnetic Resonance Imaging Using Hyperpolarized Noble Gasesxe2x80x9d, the disclosure of which is hereby incorporated by reference herein as if recited in full herein.
In order to obtain sufficient quantities of the polarized gases necessary for imaging, hyperpolarizers are used to produce and accumulate polarized noble gases. Hyperpolarizers artificially enhance the polarization of certain noble gas nuclei (such as 129Xe or 3He) over the natural or equilibrium levels, i.e., the Boltzmann polarization. Such an increase is desirable because it enhances and increases the Magnetic Resonance Imaging (xe2x80x9cMRIxe2x80x9d) signal intensity, thereby potentially allowing physicians to obtain better images of many tissues and organs in the body.
Generally stated, in order to produce the hyperpolarized gas, the hyperpolarizer is configured such that the noble gas is blended with optically pumped alkali metal vapors such as rubidium (xe2x80x9cRbxe2x80x9d). These optically pumped metal vapors collide with the nuclei of the noble gas and hyperpolarize the noble gas through a phenomenon known as xe2x80x9cspin-exchangexe2x80x9d. The xe2x80x9coptical pumpingxe2x80x9d of the alkali metal vapor is produced by irradiating the alkali-metal vapor with circularly polarized light at the wavelength of the first principal resonance for the alkali metal (e.g., 795 nm for Rb). Generally described, the ground state atoms become excited, then subsequently decay back to the ground state. Under a modest magnetic field (10 Gauss), the cycling of atoms between the ground and excited states can yield nearly 100% polarization of the atoms in a few microseconds. This polarization is generally carried by the lone valence electron characteristics of the alkali metal. In the presence of non-zero nuclear spin noble gases, the alkali-metal vapor atoms can collide with the noble gas atoms in a manner in which the polarization of the valence electrons is transferred to the noble-gas nuclei through a mutual spin flip xe2x80x9cspin-exchangexe2x80x9d.
Conventionally, lasers have been used to optically pump the alkali metals. Various lasers emit light signals over various wavelength bands. In order to improve the optical pumping process for certain types of lasers (particularly those with broader bandwidth emissions), the absorption or resonance line width of the alkali metal can be broadened to more closely correspond with the particular laser emission bandwidth of the selected laser. This broadening can be achieved by pressure broadening, i.e., by using a buffer gas in the optical pumping chamber. Collisions of the alkali metal vapor with a buffer gas can lead to a broadening of the alkali""s absorption bandwidth.
For example, it is known that the amount of polarized 129Xe which can be produced per unit time is directly proportional to the light power absorbed by the Rb vapor. Thus, polarizing 129Xe in large quantities generally takes a large amount of laser power. When using a diode laser array, the natural Rb absorption line bandwidth is typically many times narrower than the laser emission bandwidth. The Rb absorption range can be increased by using a buffer gas. Of course, the selection of a buffer gas can also undesirably impact the Rb-noble gas spin-exchange by potentially introducing an angular momentum loss of the alkali metal to the buffer gas rather than to the noble gas as desired. In any event, after the spin-exchange has been completed, the hyperpolarized gas is separated from the alkali metal prior to introduction into a patient.
Conventionally, gas-phase imaging has been possible using both 3He and 129Xe, and has been particularly useful in producing ventilation-driven images of the lungs, a region where proton images have produced signal voids. However, in contrast to gas phase imaging, dissolved phase imaging has proven to be problematic. Dissolved phase imaging uses the solubility characteristic of 129Xe in blood and lipid rich tissue. The gas phase is thus absorbed or xe2x80x9cdissolvedxe2x80x9d into surrounding tissue or blood vessels and may allow perfusion imaging of the brain, lung, or other regions. Such images can potentially allow for the performance of non-invasive studies of the pulmonary vasculature to detect emboli and other circulatory system problems. Unfortunately, once the polarized gas has been dissolved (such as into the blood vessels), it has proven difficult to generate clinically useful images using the dissolved phase gas. Conventionally, dissolved phase imaging is attempted by performing a gas-based xe2x80x9cregularxe2x80x9d image and then looking for a spatially shifted dissolved phase image. However, the small flip angles typically associated with the xe2x80x9cregularxe2x80x9d image excitation pulses generally fail to produce sufficient detectable signal spectra in the dissolved phase, thus generating relatively inadequate dissolved phase images.
For example, MRI images using gas-space-imaging techniques have been generated using hyperpolarized 129Xe gas. See Mugler III et al., MR Imaging and Spectroscopy Using Hyperpolarized 129Xe gas: Preliminary Human Results, 37 Magnetic Resonance in Medicine, pp. 809-815 (1997). While good correlation is seen between the gas-space signal in the xenon images and the gas-space signal void in the proton images, the spectra associated with the dissolved phase signal components were significantly lower than the gas-phase signal.
In addition, conventional imaging with MRI units generally requires relatively large magnetic fields. For example, 1.5 Tesla (xe2x80x9cTxe2x80x9d) units are common. The large magnetic fields can require special housing and shielding within the use site. Further, the MRI units must typically shim or control the magnetic field in order to produce magnet homogeneity which is suitable for imaging. As noted above, high field strength magnets generally require special handling ad have relatively high operating costs. Unfortunately and disadvantageously, both the high field strength magnet and the relatively high homogeneity requirements can increase the unit""s cost both to the medical facility and ultimately, the consumer.
In view of the foregoing, it is an object of the present invention to detect and/or manipulate dissolved-phase 129Xe signals in a manner that yields clinically useful images.
It is another object of the present invention to provide an imaging method which can obtain useful images of dissolved 129Xe in the pulmonary and/or cardiac vasculature.
It is an additional object of the present invention to provide an imaging method which yields useful images of the heart and major cardiac vessels using dissolved polarized 129Xe.
It is yet another object of the present invention to provide an imaging method which can obtain useful information and/or images of dissolved 129Xe which does not require high magnetic field strength and/or high magnetic field homogeneity.
It is a further object of the present invention to be able to obtain real-time blood flow path information such as local perfusion variation or blood flow abnormality using MR spectroscopy.
It is yet a further object of the present invention to provide an imaging method which can be used to determine quantitative measures of perfusion using dissolved polarized 129Xe.
These and other objects are satisfied by the present invention, which uses large flip angle (such as 90xc2x0) RF excitation pulses to excite dissolved phase gas in the pulmonary vasculature and MR data image acquisition techniques. In particular, a first aspect of the invention is directed to a method for obtaining MRI images using dissolved polarized 129Xe. The method includes positioning a patient in an MRI apparatus having a magnetic field associated therewith. Polarized 129Xe gas is delivered to the pulmonary region of the patient""s body. Preferably, the 129Xe is inhaled and, due to the relatively high solubility of 129Xe, in a relatively short period of time, the inhaled polarized 129Xe gas enters into the body in the lung air spaces and either exists in the lung space as a gas and/or a gas which dissolves into adjacent vasculature, tissues, spaces, or organs. Thus, the solubility of polarized 129Xe in the body is such that it generates an associated hyperpolarized gas imaging phase and a hyperpolarized dissolved imaging phase. A predetermined region (i.e., a region of interest) of the patient""s body which has a portion of the dissolved phase polarized gas therein is excited with a large angle (e.g. 90 degree) excitation pulse. At least one MRI image associated with the dissolved phase polarized gas is acquired after the excitation pulse. In a preferred embodiment, a multi-echo pulse sequence is used to generate an MR image. Further preferably, the excitation step is repeated within a predetermined repetition time. It is also preferred that the exciting step is performed so that the large angle pulse selectively excites substantially only the dissolved phase of the 129Xe.
Another aspect of the present invention is a method for evaluating (e.g., measuring, determining, quantifying, observing, monitoring, imaging and/or assessing) the blood flow of a patient. A patient or subject having a pulmonary and cardiac vasculature is positioned in a MR (magnetic resonance) spectroscopy system. Polarized gaseous 129Xe is delivered to the patient or subject. The pulmonary and cardiac vasculature has an associated blood flow path and a portion of the polarized gaseous 129Xe is dissolved into the pulmonary (and/or cardiac) vasculature blood flow path. The blood flow of the subject can be evaluated (to determine, e.g., xenon enhanced perfusion deficits, blood flow rate, blood volume, or blood flow path blockage) based on the spectroscopic signal of the dissolved 129Xe in the pulmonary (and/or cardiac) vasculature (i.e., a portion of the circulatory system""s blood flow path between and including at least portions of the lungs and heart). Preferably the evaluating step includes a measuring step and blood flow path blockage can be detected by comparing the blood flow rates of healthy subjects with the subject""s measured flow rate.
An additional aspect of the present invention is directed toward a cardiac imaging method. The method includes positioning a subject in an MRI system and delivering polarized 129Xe thereto. At least a portion of the polarized 129Xe is dissolved into the cardiac blood flow path of the subject. The dissolved polarized 129Xe is excited with a large angle RF excitation pulse and a MR image associated with the excited dissolved polarized 129Xe is generated. Preferably, the excitation pulse is selectively delivered to a target area along the cardiac blood flow path and is spatially limited to limit the depolarizing affect on the polarized gaseous 129Xe outside the target region.
Advantageously, unlike imaging the gas-phase 129Xe in the lung where conventionally small flip angles are used to avoid destroying the available 129Xe magnetization, there is minimal or no penalty for using a large flip angle excitation of the dissolved phase 129Xe because it will otherwise flow out of the chest region un-imaged. Indeed, a rapid large angle (such as 90 degree) pulse imaging sequence makes optimal use of the dissolved magnetization. The excitation repetition rate should be fast enough to capture the 129Xe before it flows out of the chest region. Such an imaging method can provide useful two (2) and three (3) dimensional dissolved phase images of the pulmonary and cardiac vasculature, images of anatomical features along the cardiac blood flow path, and patient blood flow rates and potential defects in the structure along the blood flow path of interest.
Further advantageously, blood flow abnormalities, perfusion variations (deficits or increases) and blood flow rate evaluation methods in spectroscopic systems according to the instant invention can be used in MRI units with reduced magnetic fields (such as 0.15 Tesla) and less restrictive homogeneity requirements. Further, the instant invention can use spectroscopic or MRI imaging techniques to obtain signal data corresponding to a quantity of dissolved polarized 129Xe before and after a physiologically active substance is administered to a human or animal body to evaluate the efficacy of the drug treatment or to quantitatively analyze a subject""s blood flow.
The foregoing and other objects and aspects of the present invention are explained in detail herein.